Acatalasemic mice are mildly susceptible to adriamycin nephropathy and exhibit increased albuminuria and glomerulosclerosis

BMC Nephrology

Research Article

Hiroshi Morinaga¹  Hitoshi Sugiyama¹  Noriyoshi Masuoka²  Shinji Kitamura³  Hirofumi Makino³  Yohei Maeshima³  Yoko Kikumoto³  Masashi Kitagawa³  Keiichi Takiue³  Tatsuyuki Inoue⁴  Da-Hong Wang⁵  Keiki Ogino⁵ 

[1] Center for CKD and Peritoneal Dialysis, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, 700-8558, Okayama, Japan;Department of Life Science, Okayama University of Science, 1-1, Ridai-cho, Kita-ku, 700-0005, Okayama, Japan;Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, 700-8558, Okayama, Japan;Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, 700-8558, Okayama, Japan;Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan;Public Health, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, 700-8558, Okayama, Japan;

关键词: Catalase;    Catalase Activity;    Glomerulosclerosis;    Urinary Albumin Excretion;    Tubulointerstitial Injury;   

DOI  :  10.1186/1471-2369-13-14

 received in 2011-10-22, accepted in 2012-03-25,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundCatalase is an important antioxidant enzyme that regulates the level of intracellular hydrogen peroxide and hydroxyl radicals. The effects of catalase deficiency on albuminuria and progressive glomerulosclerosis have not yet been fully elucidated. The adriamycin (ADR) nephropathy model is considered to be an experimental model of focal segmental glomerulosclerosis. A functional catalase deficiency was hypothesized to exacerbate albuminuria and the progression of glomerulosclerosis in this model.MethodsADR was intravenously administered to both homozygous acatalasemic mutant mice (C3H/AnLCsbCsb) and control wild-type mice (C3H/AnLCsaCsa). The functional and morphological alterations of the kidneys, including albuminuria, renal function, podocytic, glomerular and tubulointerstitial injuries, and the activities of catalase were then compared between the two groups up to 8 weeks after disease induction. Moreover, the presence of a mutation of the toll-like receptor 4 (tlr4) gene, which was previously reported in the C3H/HeJ strain, was investigated in both groups.ResultsThe ADR-treated mice developed significant albuminuria and glomerulosclerosis, and the degree of these conditions in the ADR-treated acatalasemic mice was higher than that in the wild-type mice. ADR induced progressive renal fibrosis, renal atrophy and lipid peroxide accumulation only in the acatalasemic mice. In addition, the level of catalase activity was significantly lower in the kidneys of the acatalasemic mice than in the wild-type mice during the experimental period. The catalase activity increased after ADR injection in wild-type mice, but the acatalasemic mice did not have the ability to increase their catalase activity under oxidative stress. The C3H/AnL strain was found to be negative for the tlr4 gene mutation.ConclusionsThese data indicate that catalase deficiency plays an important role in the progression of renal injury in the ADR nephropathy model.

【 授权许可】

Unknown   
© Takiue et al; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.